Nivolumab With and Without Ipilimumab and Radiation Therapy in Treating Patients With Recurrent or Resectable Undifferentiated Pleomorphic Sarcoma or Dedifferentiated Liposarcoma Before Surgery

NCT03307616 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2017-0143NCI-2018-01031
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well nivolumab with and without ipilimumab and radiation therapy when given before surgery works in treating patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma that can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may work better in treating patients with undifferentiated pleomorphic sarcoma.

Conditions

Dedifferentiated Liposarcoma; Recurrent Dedifferentiated Liposarcoma; Recurrent Undifferentiated Pleomorphic Sarcoma; Resectable Dedifferentiated Liposarcoma; Resectable Undifferentiated Pleomorphic Sarcoma; Undifferentiated Pleomorphic Sarcoma

Outcome Measures

Primary Outcomes (1)

• Pathologic response

  Pathologic response will be assessed at time of surgical resection by percentage hyalinization. The study will estimate the difference of the pathologic response between the treatment arms (A versus \[vs\] B, C vs D) along with the estimate of variation of the difference. Given the longitudinal nature of the data, linear mixed effect models for longitudinal measures will be employed to assess the change in the magnitude of the measures over time adjusting for multiple covariates including patient's characteristics, and tumor characteristics. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

  At day 43 (Arm A/B) or 71 (Arm C/D)

Secondary Outcomes (7)

• Assessment of immunologic changes in the tumor microenvironment and blood

  Up to 2 years

• Change in Immune Infiltrate in Response to Neoadjuvant Nivolumab Monotherapy and Neoadjuvant Nivolumab and Ipilimumab Combination Therapy

  Up to 2 years

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0

  Up to 100 days

• Recurrence-free survival (RFS)

  At 12 and 24 months

• Overall survival (OS)

  At 12 and 24 months

Study Arms (4)

Arm A (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 1 hour on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43.

Biological: Nivolumab

Arm B (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab as in Arm A. Patients also receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 43.

Biological: Ipilimumab; Biological: Nivolumab

Arm C (nivolumab, RT)

EXPERIMENTAL

Patients receive nivolumab IV over 1 hour on days 1, 15, 29, and 43. Patients also undergo RT QD for 5 days during days 15-47 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71.

Biological: Nivolumab; Radiation: Radiation Therapy

Arm D (nivolumab, ipilimumab, RT)

EXPERIMENTAL

Patients receive nivolumab as in Arm C, ipilimumab as in Arm B, and RT as in Arm C in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery within 2 weeks after day 71.

Biological: Ipilimumab; Biological: Nivolumab; Radiation: Radiation Therapy

Interventions

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Arm C (nivolumab, RT); Arm D (nivolumab, ipilimumab, RT)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm B (nivolumab, ipilimumab); Arm D (nivolumab, ipilimumab, RT)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (nivolumab); Arm B (nivolumab, ipilimumab); Arm C (nivolumab, RT); Arm D (nivolumab, ipilimumab, RT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Patients must have disease determined to be surgically resectable and candidates for upfront surgery as agreed upon by a multidisciplinary consensus (Surgical Oncology, Medical Oncology, Radiation Oncology) after presentation at sarcoma multidisciplinary conference. Resectable tumors are defined as having no significant vascular, neural or bony involvement. Only cases where a complete surgical resection can safely be achieved are defined as resectable.
• Patients will be evaluated by the anesthesia team prior to surgery.
• Patient must have recent imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\], as appropriate) within 4 weeks of trial enrollment, demonstrating measurable disease as defined by RECIST 1.1.
• Patients must have at least one tumor amenable to serial biopsy in clinic or be willing to undergo serial biopsies through image-guided procedures during the neoadjuvant phase of the protocol. Patients must be willing to provide tumor samples at the time points.
• Patients must be medically fit to undergo surgery as determined by the treating medical and surgical oncology team and have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must have life expectancy \> 6 months.
• Patients must be immunotherapy-naive. Those who have previously been treated with conventional chemotherapy for a prior history of sarcoma in the adjuvant setting may be included.
• White blood cell count \> 3 K/uL.
• Absolute neutrophil count (ANC) \> 1 K/uL.
• Hemoglobin \> 9 g/dL.
• Platelets \> 100 K/mm\^3.
• Serum creatinine =\< 2 mg/dL OR creatinine clearance \> 50 mL/min.
• Aspartic transaminase (AST) =\< 1.5 x upper limit of normal (ULN).
• Alanine transaminase (ALT) =\< 1.5 x ULN.

You may not qualify if:

• Disease that is considered surgically unresectable, including, but not limited to significant vascular, neural, or bone involvement, and in cases where a complete surgical resection cannot be safely performed.
• Prior intra-abdominal surgery within 4 weeks of trial enrollment.
• Prior chemotherapy or targeted small molecule therapy of the current sarcoma. In patients with locally recurrent disease, previous systemic chemotherapy of the primary tumor is allowed, as long as treatment was completed prior to study enrollment and patient has recovered (i.e., \< grade 1 or at baseline) from any adverse events due to previously administered agents.
• Prior radiation therapy for sarcoma in the same area.
• Active concurrent second malignancy.
• Prior or concurrent immunotherapy, including treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody; tumor vaccines; interferon, or interleukins.
• Prior malignancy active within the previous 2 years except for patient's prior diagnosis of sarcoma and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation).
• Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment.
• Pregnant or lactating female.
• Unwillingness or inability to follow the procedures required in the protocol.
• Current use of anticoagulants (warfarin, heparin, direct thrombin inhibitors) at therapeutic levels.
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Brief dosing for contrast allergy prophylaxis is allowed.
• Any positive test result for hepatitis B or C virus indicating acute or chronic infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Keung EZ, Lazar AJ, Torres KE, Wang WL, Cormier JN, Ashleigh Guadagnolo B, Bishop AJ, Lin H, Hunt KK, Bird J, Lewis VO, Patel SR, Wargo JA, Somaiah N, Roland CL. Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. BMC Cancer. 2018 Sep 24;18(1):913. doi: 10.1186/s12885-018-4829-0.

  PMID: 30249211 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Liposarcoma; Histiocytoma, Malignant Fibrous

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Therapeutics; Physical Phenomena

Study Officials

• Christina L Roland

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 12, 2017
• Study Start: October 4, 2017
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)